Morphine tolerance and dependence in the nociceptin receptor knockout mice

T. Mamiya, Y. Noda, X. Ren, T. Nagai, H. Takeshima, M. Ukai, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor knockout mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor knockout mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor knockout mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor knockout mice, the jumping signs in the nociceptin receptor knockout mice were less severe than those in wild-type mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor knockout mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor knockout mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.

Original languageEnglish
Pages (from-to)1349-1361
Number of pages13
JournalJournal of Neural Transmission
Volume108
Issue number12
DOIs
Publication statusPublished - 01-12-2001
Externally publishedYes

Fingerprint

Morphine Dependence
Knockout Mice
Morphine
Cyclic AMP
Thalamus
nociceptin receptor
mu Opioid Receptor
Naloxone
naloxone benzoylhydrazone

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Mamiya, T. ; Noda, Y. ; Ren, X. ; Nagai, T. ; Takeshima, H. ; Ukai, M. ; Nabeshima, Toshitaka. / Morphine tolerance and dependence in the nociceptin receptor knockout mice. In: Journal of Neural Transmission. 2001 ; Vol. 108, No. 12. pp. 1349-1361.
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Mamiya, T, Noda, Y, Ren, X, Nagai, T, Takeshima, H, Ukai, M & Nabeshima, T 2001, 'Morphine tolerance and dependence in the nociceptin receptor knockout mice', Journal of Neural Transmission, vol. 108, no. 12, pp. 1349-1361. https://doi.org/10.1007/s007020100012

Morphine tolerance and dependence in the nociceptin receptor knockout mice. / Mamiya, T.; Noda, Y.; Ren, X.; Nagai, T.; Takeshima, H.; Ukai, M.; Nabeshima, Toshitaka.

In: Journal of Neural Transmission, Vol. 108, No. 12, 01.12.2001, p. 1349-1361.

Research output: Contribution to journalArticle

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Mamiya T, Noda Y, Ren X, Nagai T, Takeshima H, Ukai M et al. Morphine tolerance and dependence in the nociceptin receptor knockout mice. Journal of Neural Transmission. 2001 Dec 1;108(12):1349-1361. https://doi.org/10.1007/s007020100012